Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, LE1 9HN UK.
Mol Cell Neurosci. 2011 Sep;48(1):51-61. doi: 10.1016/j.mcn.2011.06.005. Epub 2011 Jun 25.
Exposure to intense sound can cause damage to the delicate sensory and neuronal components of the cochlea leading to hearing loss. Such damage often causes the dendrites of the spiral ganglion neurons (SGN), the neurons that provide the afferent innervation of the hair cells, to swell and degenerate thus damaging the synapse. In models of neuropathic pain, axotomy, another form of afferent nerve damage, is accompanied by altered voltage-gated sodium channel (VGSC) expression, leading to neuronal hyperactivity. In this study, adult Wistar rats were exposed to noise which produced a mild, 20 dB hearing threshold elevation and their VGSC expression was investigated. Quantitative PCR showed decreased Na(V)1.1 and Na(V)1.6 mRNA expression in the SGN following noise exposure (29% and 56% decrease respectively) while Na(V)1.7 mRNA expression increased by approximately 20% when compared to control rats. Immunohistochemistry extended these findings, revealing increased staining for Na(V)1.1 along the SGN dendrites and Na(V)1.7 in the cell bodies after noise. These results provide the first evidence for selective changes in VGSC expression following moderate noise-induced hearing loss and could contribute to elevated hearing thresholds and to the generation of perceptual anomalies commonly associated with cochlear damage, such as tinnitus and hyperacusis.
暴露在强烈的声音中会导致耳蜗中精细的感觉和神经元成分受损，从而导致听力损失。这种损伤通常会导致螺旋神经节神经元（SGN）的树突肿胀和退化，从而损伤突触。在神经病理性疼痛模型中，轴突切断（另一种传入神经损伤形式）伴随着电压门控钠离子通道（VGSC）表达的改变，导致神经元过度兴奋。在这项研究中，成年 Wistar 大鼠暴露于噪声中，导致听力阈值轻度升高 20dB，并对其 VGSC 表达进行了研究。定量 PCR 显示，噪声暴露后 SGN 中的 Na(V)1.1 和 Na(V)1.6 mRNA 表达减少（分别减少 29%和 56%），而 Na(V)1.7 mRNA 表达增加了约 20%与对照大鼠相比。免疫组织化学进一步证实了这些发现，即在噪声后 SGN 树突中 Na(V)1.1 染色增加，在细胞体中 Na(V)1.7 染色增加。这些结果首次提供了中度噪声性听力损失后 VGSC 表达选择性变化的证据，可能导致听力阈值升高，并产生与耳蜗损伤相关的感知异常，如耳鸣和听觉过敏。
